Longitudinal RNA-Seq Analysis of Vertebrate Aging Identifies Mitochondrial Complex I as a Small-Molecule-Sensitive Modifier of Lifespan
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Date
2016-02-24
Publication Type
Journal Article
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yes
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Abstract
Mutations and genetic variability affect gene expression and lifespan, but the impact of variations in gene expression within individuals on their aging-related mortality is poorly understood. We performed a longitudinal study in the short-lived killifish, Nothobranchius furzeri, and correlated quantitative variations in gene expression during early adult life with lifespan. Shorter- and longer-lived individuals differ in their gene expression before the onset of aging-related mortality; differences in gene expression are more pronounced early in life. We identified mitochondrial respiratory chain complex I as a hub in a module of genes whose expression is negatively correlated with lifespan. Accordingly, partial pharmacological inhibition of complex I by the small molecule rotenone reversed aging-related regulation of gene expression and extended lifespan in N. furzeri by 15%. These results support the use of N. furzeri as a vertebrate model for identifying the protein targets, pharmacological modulators, and individual-to-individual variability associated with aging.
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published
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Journal / series
Volume
2 (2)
Pages / Article No.
122 - 132
Publisher
Cell Press
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Edition / version
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Date collected
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Subject
Aging; GAGE; History trait; Hormesis; Hourglass; Life ribosome; Lifespan regulation; Longevity; Longitudinal study; Mitohormesis; Nothobranchius furzeri; Rejuvenation; RNA transport; RNA-seq; Weighted gene coexpression network analysis (WGCNA); Zebrafish
Organisational unit
03976 - Ristow, Michael (ehemalig) / Ristow, Michael (former)